|Year : 2021 | Volume
| Issue : 1 | Page : 51-54
Granulocytic sarcoma: A case series and review
M .P Rakesh1, Nizar Mullali Mohamed Kunhi2, Niranjan Vijayaraghavan1, KV S. Latha1
1 Department of Medical Oncology, Madras Medical College, Chennai, Tamil Nadu, India
2 IQRAA International Hospital and Research Center, Kozhikode, Kerala, India
|Date of Submission||08-Aug-2020|
|Date of Decision||11-Sep-2020|
|Date of Acceptance||18-Sep-2020|
|Date of Web Publication||15-Mar-2021|
Dr. Niranjan Vijayaraghavan
Department of Medical Oncology, Madras Medical College, Chennai - 600 003, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Granulocytic sarcomas (GSs) are rare, solid, extramedullary tumors composed of immature myeloid cells. They can be seen before, concomitantly with or after a diagnosis of acute myeloid leukemia, chronic myeloid leukemia, or myelodysplastic syndromes. We report four unusual presentations of granulocytic sarcoma treated at our center. Due to the rarity of the disease, it is difficult to conduct randomized controlled trials, and hence, there are no consensus for the treatment of GS. Most of the isolated GS frequently progress to acute myeloid leukemia, and all GSs tend to have a poor prognosis.
Keywords: Acute myeloid leukemia, chemotherapy, chronic myeloid leukemia, granulocytic sarcoma, imatinib
|How to cite this article:|
Rakesh M ., Mohamed Kunhi NM, Vijayaraghavan N, S. Latha K V. Granulocytic sarcoma: A case series and review. J Appl Hematol 2021;12:51-4
| Introduction|| |
Granulocytic sarcomas (GSs) are rare, solid, extramedullary tumors composed of immature myeloid cells. Other commonly used terminologies include chloroma, myeloid sarcoma, myeloblastoma, and extramedullary myeloid tumor. GS is considered as a subgroups of myeloid neoplasms and acute leukemia in the WHO classification. They can be seen before, concomitantly with or after a diagnosis of acute myeloid leukemia (AML), chronic myeloid leukemia (CML), or myelodysplastic syndromes. GS can rarely be seen in isolation when they are termed as isolated GS. They closely mimic lymphomas, poorly differentiated carcinomas, and extramedullary hemopoiesis, and hence, good knowledge of its histopathology with immunohistochemical backup is necessary for an accurate diagnosis. All GS tend to have a poor prognosis, and most of the isolated GS frequently progress to acute myeloid leukemia. Since it is a rare disease, mainly case reports are reported in the literature. Hence, there are no consensus on the treatment of GS. Here, we report four unusual presentations of GS who were diagnosed and treated at our center.
| Case Reports|| |
A 74-year-old male, with no significant past medical history noticed swelling over the left shoulder of 2 months duration with progressive increase in its size. He also felt progressive tiredness. His clinical examination revealed nothing other than the fluctuant swelling on posterolateral aspect of the trunk below the left shoulder [Figure 1]. Aspiration cytology of the lesion revealed clusters and singly scattered myeloid precursors with various stages of maturation comprising of myelocytes, band forms, neutrophils, and occasional eosinophils in a serofibrinous background suggestive of myeloid sarcoma [Figure 2]. Further evaluation of his peripheral smear [Figure 3] revealed blasts –4%, promyelocyte –1%, myelocyte –18%, metamyelocyte –13%, band forms –15%, neutrophils –38%, eosinophilic precursors – 8%, and basophils –3% suggestive of CML-chronic phase (CML-CP). A subsequent bone marrow aspiration study also favored a diagnosis of CML-CP with markedly increased reticulin fibrosis. Fluorescence in situ hybridization was positive for BCR-ABL in 90% of interphase cells. In view of the age and poor performance status of the patient, imatinib was started instead of anthracycline- and cytarabine-based chemotherapy along with best supportive care. The swelling reduced in size within 30 days of starting the treatment along with the improvement in general well-being of the patient. He is still under close follow-up with us tolerating imatinib with no new symptoms.
|Figure 1: Picture shows an ill-defined mass in the posterolateral aspect of the trunk below the left shoulder. Consent obtained from the patient for using the clinical picture|
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|Figure 2: Aspirate from the swelling shows myeloid maturation cells including blasts in a serofibrinous background suggestive of myeloid sarcoma. Giemsa stain ×40|
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|Figure 3: Peripheral smear shows spectrum of myeloid maturation cells including blasts basophils. Giemsa stain ×100|
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A 32-year-old male with no comorbidities developed severe headache and projectile vomiting. His brain magnetic resonance imaging (MRI) revealed large cystic lesion in the temporoparietal lobe with mass effect and perilesional edema. He underwent left temporoparietal craniotomy and excision of the mass. The histopathology revealed cystic space-occupying lesion with hemorrhagic necrosis and features of extramedullary hematopoiesis. Further evaluation revealed a normal peripheral smear while bone marrow showed 1% blasts, promyelocytes –19%, metamyelocyte and band form –34%, and neutrophils –30% suggestive of CML-CP. He was started on cytarabine- and anthracycline-based induction along with tablet imatinib and achieved remission; however, he failed to maintain follow-up 3 months after the last cycle.
A 4-year-old girl presented with progressive swelling of the right eye with no other symptoms. She was born out of a nonconsanguineous marriage as a third child. The delivery was uneventful. MRI brain showed soft-tissue density lesion in the superior and preseptal region of right orbit, extending into retrobulbar space. A well-defined broad base isointense lesion with surrounding edema noted involving left cerebellum causing mass effect laterally on vermis, superiorly on pons and occludes the transverse and proximal sigmoid sinus. She underwent subfrontal craniotomy near total excision of cerebellar SOL and VP shunt. Histopathology showed a cellular-infiltrating neoplasm composed of uniform small round cells with deep staining nuclei, some had prominent nucleoli. The cells were CD 33, CD 56, CD 117, and myeloperoxidase positive, suggesting the possibility of dural-based myeloid sarcoma. The peripheral smear and bone marrow aspiration of the patient were normal. She succumbed to the illness in the postoperative period.
A 5-year-old boy presented with proptosis right eye of 3 months duration. He was born out of a nonconsanguineous marriage, and the delivery was uneventful. Brain imaging showed a well-defined retrobulbar mass in right orbit. Biopsy from the lesion showed sheets of round-to-oval cells with vacuolated cytoplasm and moderate eosinophilic cytoplasm. The immunohistochemistry showed CD33 and myeloperoxidase positive with negative markers for lymphoma giving a diagnosis of granulocytic sarcoma. Further evaluation revealed a normal peripheral smear and bone marrow aspiration studies. The patient received cytarabine- and daunorubicin-based induction chemotherapy. However, there was a prolonged period of aplasia following induction and developed progressive respiratory infection and succumbed to the illness.
| Discussion|| |
GSs have been reported in various organ systems, including central nervous system (CNS), skin, gastrointestinal, genitourinary, lymphatic, musculoskeletal, and breast.,,, Three out of the four cases reported here are of CNS involvement, while the other has skin involvement. As per the WHO classification, GSs are divided into three types based on the degree of maturation. Blastic type, which consists of myeloblast, immature type, which consist of myeloblast and promyelocyte, and differentiated type, which has promyelocyte and mature myeloid cells.
Most GS occur concurrently with myeloid neoplasm. Around 2% to 8% of AML patients have GS. They can occur as a solitary or multifocal tumor. It can occur before the diagnosis of AML or diagnosed concomitantly with AML or subsequent to the diagnosis of AML.,,,, Two of our cases reported above had a concurrent myeloid neoplasm while the other 2 were in isolation.
The pathophysiology of isolated GS is not fully understood and whether isolated GS and GS represent the same disease is a matter of uncertainty. For instance, in a case reported by Lillington et al., the patient was diagnosed to have a GS with a normal marrow. However, the cells in marrow as well as the GS had the same molecular and cytogenic abnormality highlighting presence of occult myeloid disease despite a normal marrow. This indicates that isolated GS and GS could be in the same disease spectrum. The most common differential diagnosis for a GS is a lymphoma followed by malignant melanoma, undifferentiated cancer, and extramedullary hematopoiesis.,, A sound histopathological knowledge and clinical suspicion are necessary for an accurate and early diagnosis.
The occurrence of myeloid sarcoma or extramedullary disease suggests that there might be an aberrant homing signal for the leukemic blasts. Faaij et al. had identified the chemokine receptors that play a significant role in homing and retention of AML blasts in the skin, namely CXCR4, CCR5, CXCR7, and CXCR3. There is also evidence of matrix metalloproteinase 9 interacting with beta 2 integrin for migration of AML derived cells. There are evidences which support that leukemic cell express CD 56 which is neural cell adhesion molecule might predispose to CNS homing of the leukemic cells., However, CD56 is more frequently seen in cases with skin involvement.
GS can occur in patients with CML. In patient 1 and 2, the initial presentation of a soft-tissue myeloid sarcoma led to the diagnosis of an underlying CML in blast crisis. The excess of reticulin fibers in the bone marrow of patient 1 suggested the disease had been present in a CP for some time. The diagnosis of CML in blast crisis could have missed or would not have made if not for the detection of myeloid sarcoma in otherwise asymptomatic patients 1 and 2.
Due to the rarity of the disease, it is difficult to conduct randomized controlled trials, and hence, there are no consensus for the treatment of GS. The treatment for both isolated GS and GS with concomitant AML is chemotherapy protocols used for treating AML. This is based on the observation that a higher proportion of patients with isolated GS progresses to AML while receiving only local therapy when compared to those patients receiving systemic therapy., However, the data regarding the preferred regimen for treating GS are very minimal. The patient 1 was started on imatinib 400 mg once daily and showed a dramatic improvement in symptoms and reduction in the size of the swelling within a period of 30 days, whereas patients 2 & 4 were started of anthracycline- and cytarabine-based chemotherapy and treated as blast crisis.
| Conclusion|| |
There are century old literature describing GSs, but none of them could validate the occurrence of the disease in a small proportion of AML/CML patients, and its temporal association with the disease still remains a topic for discussion. Here, we highlight four different presentations of GSs as well as the underlying disease for which all four were asymptomatic otherwise. The patients with isolated GS might have a slightly better prognosis than AML patients without GS. These patients offer insights to the pathophysiologic, diagnostic, and therapeutic challenges associated with this rare disorder. A sound knowledge of the disease for a clinician and an expert pathologist is an utmost necessity for early suspicion, diagnosis, and treatment of GS.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
We would like to thank other consultants, residents of department of medical oncology who have contributed in the treatment of all the patients. We would also like to thank our department staffs for providing technical help.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Roth MJ, Medeiros LJ, Elenitoba-Johnson K, Kuchnio M, Jaffe ES, Stetler-Stevenson M. Extramedullary myeloid cell tumors. An immunohistochemical study of 29 cases using routinely fixed and processed paraffin-embedded tissue sections. Arch Pathol Lab Med 1995;119:790-8.
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al
. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: Rationale and important changes. Blood 2009;114:937-51.
Pileri SA, Ascani S, Cox MC, Campidelli C, Bacci F, Piccioli M, et al
. Myeloid sarcoma: Clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia 2007;21:340-50.
Lan TY, Lin DT, Tien HF, Yang RS, Chen CY, Wu K. Prognostic factors of treatment outcomes in patients with granulocytic sarcoma. Acta Haematol 2009;122:238-46.
Cunningham I. Extramedullary sites of leukemia relapse after transplant. Leuk Lymphoma 2006;47:1754-67.
Yamauchi K, Yasuda M. Comparison in treatments of nonleukemic granulocytic sarcoma: Report of two cases and a review of 72 cases in the literature. Cancer 2002;94:1739-46.
Suh YK, Shin HJ. Fine-needle aspiration biopsy of granulocytic sarcoma: A clinicopathologic study of 27 cases. Cancer Cytopathol 2000;90:364-72.
Jaffe ES, editor. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Iarc: IARC press; 2001.
Tsimberidou AM, Kantarjian HM, Wen S, Keating MJ, O'Brien S, Brandt M, et al
. Myeloid sarcoma is associated with superior event-free survival and overall survival compared with acute myeloid leukemia. Cancer 2008;113:1370-8.
Neiman RS, Barcos M, Berard C, Bonner H, Mann R, Rydell RE, et al
. Granulocytic sarcoma: A clinicopathologic study of 61 biopsied cases. Cancer 1981;48:1426-37.
Lillington DM, Jaju RJ, Shankar AG, Neat M, Kearney L, Young BD, et al
. Cytogenetic and molecular evidence of marrow involvement in extramedullary acute myeloid leukaemia. Br J Haematol 2000;110:547-51.
Paydas S, Zorludemir S, Ergin M. Granulocytic sarcoma: 32 cases and review of the literature. Leuk Lymphoma 2006;47:2527-41.
Faaij CM, Willemze AJ, Révész T, Balzarolo M, Tensen CP, Hoogeboom M, et al
. Chemokine/chemokine receptor interactions in extramedullary leukaemia of the skin in childhood AML: Differential roles for CCR2, CCR5, CXCR4 and CXCR7. Pediatr Blood Cancer 2010;55:344-8.
Stefanidakis M, Karjalainen K, Jaalouk DE, Gahmberg CG, O'Brien S, Pasqualini R, et al
. Role of leukemia cell invadosome in extramedullary infiltration. Blood 2009;114:3008-17.
Byrd JC, Weiss RB, Arthur DC, Lawrence D, Baer MR, Davey F, et al
. Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): Results from Cancer and Leukemia Group B 8461. J Clin Oncol 1997;15:466-75.
Psiachou-Leonard E, Paterakis G, Stefanaki K, Mikraki-Christou V, Haidas S. Cerebellar granulocytic sarcoma in an infant with CD56+ acute monoblastic leukemia. Leuk Res 2001;25:1019-21.
[Figure 1], [Figure 2], [Figure 3]